Abstract
BackgroundTrials of intermittent preventive treatment against malaria in infants (IPTi) using sulphadoxine-pyrimethamine (SP) have shown a positive, albeit variable, protective efficacy against clinical malaria episodes. The impact of IPTi in different epidemiological settings and over time is unknown and predictions are hampered by the lack of knowledge about how IPTi works. We investigated mechanisms proposed for the action of IPTi and made predictions of the likely impact on morbidity and mortality.Methods/Principal FindingsWe used a comprehensive, individual-based, stochastic model of malaria epidemiology to simulate recently published trials of IPTi using SP with site-specific characteristics as inputs. This baseline model was then modified to represent hypotheses concerning the duration of action of SP, the temporal pattern of fevers caused by individual infections, potential benefits of avoiding fevers on immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The baseline model reproduced the pattern of results reasonably well. None of the models based on alternative hypotheses improved the fit between the model predictions and observed data. Predictions suggest that IPTi would have a beneficial effect across a range of transmission intensities. IPTi was predicted to avert a greater number of episodes where IPTi coverage was higher, the health system treatment coverage lower, and for drugs which were more efficacious and had longer prophylactic periods. The predicted cumulative benefits were proportionately slightly greater for severe malaria episodes and malaria-attributable mortality than for acute episodes in the settings modelled. Modest increased susceptibility was predicted between doses and following the last dose, but these were outweighed by the cumulative benefits. The impact on transmission intensity was negligible.ConclusionsThe pattern of trial results can be accounted for by differences between the trial sites together with known features of malaria epidemiology and the action of SP. Predictions suggest that IPTi would have a beneficial impact across a variety of epidemiological settings.
Highlights
Intermittent preventive treatment in infants (IPTi) involves giving antimalarial drugs at scheduled times during the first year of life, irrespective of whether the infants have malaria infections [1]
Trial characteristics which have been highlighted are levels of drug resistance, transmission intensity, seasonality, IPTi schedule, and other interventions for malaria control (such as insecticide-treated nets (ITN) and treatment coverage) [2,3,4]. We use these characteristics as inputs to a stochastic simulation model of malaria epidemiology
Model 1 (Baseline model): Model of malaria epidemiology taking into account between-trial differences
Summary
Intermittent preventive treatment in infants (IPTi) involves giving antimalarial drugs at scheduled times during the first year of life, irrespective of whether the infants have malaria infections [1]. Trial characteristics which have been highlighted are levels of drug resistance, transmission intensity, seasonality, IPTi schedule, and other interventions for malaria control (such as insecticide-treated nets (ITN) and treatment coverage) [2,3,4]. We use these characteristics as inputs to a stochastic simulation model of malaria epidemiology. We use the model which best fits our criteria to make predictions of the impact of IPTi in different epidemiological settings and with varying drug characteristics. We investigated mechanisms proposed for the action of IPTi and made predictions of the likely impact on morbidity and mortality
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